Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade
Contribution of large-sized primary sensory neuronal sensitization to mechanical allodynia by upregulation of hyperpolarization-activated cyclic nucleotide gated channels via cyclooxygenase 1 cascade
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通过环氧合酶 1 级联上调超极化激活的环核苷酸门控通道，导致大尺寸初级感觉神经元敏化对机械异常性疼痛的贡献
DOI：
10.1016/j.neuropharm.2016.10.012
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发表时间：
2017-02
影响因子：
4.7
通讯作者：
Chen Jun
中科院分区：
文献类型：
--
作者：
Sun Wei;Yang Fei;Wang Yan;Fu Han;Yang Yan;Li Chun-Li;Wang Xiao-Liang;Lin Qing;Chen Jun
在生理状态下，背根神经节（DRG）的小、中型神经元被认为是介导疼痛刺激的伤害性行为反应的神经元。然而，最近发现，一些大尺寸的神经元也参与神经病理条件下的伤害性传递。然而，大尺寸DRG神经元介导伤害性感受的潜在机制知之甚少。本研究旨在探讨大神经元在蜂毒诱导的机械性痛觉超敏反应中的作用及其机制。在行为学上，我们发现，在化学方法去除瞬时受体电位香草酸1阳性DRG神经元的大鼠中，BV注射仍然诱发机械性异常性疼痛。在电生理上，在体外膜片钳记录的大尺寸的神经元显示这些神经元的超兴奋性。有趣的是，这些神经元的放电模式由阶段性的BV炎症状态下的紧张性。已经表明，在大尺寸DRG神经元中表达的超极化激活的环核苷酸门控通道（HCN）对重复放电做出重要贡献。因此，我们研究了HCN在BV诱导的机械性异常性疼痛中的作用。与免疫荧光检测到的HCN 1/2过表达一致，BV处理的样品中HCN介导的超极化激活阳离子电流（Ih）显著增加。药理学实验表明，大神经元的高兴奋性和I的上调是通过环氧合酶-1（考克斯-1）-前列腺素E2途径介导的。考克斯-1抑制剂显著减弱BV诱导的机械性异常性疼痛的事实证明了这一点。这些结果表明BV至少部分通过激活考克斯-1增加Ih来兴奋DRG大尺寸神经元。
Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically,in vitropatch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in BV-induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (Ih) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation ofIhin large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasingIhthrough activation of COX-1.
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影响因子：
82.9
作者：
Xu ZZ;Kim YH;Bang S;Zhang Y;Berta T;Wang F;Oh SB;Ji RR
通讯作者：
Ji RR
影响因子：
64.5
作者：
Rutlin M;Ho CY;Abraira VE;Cassidy C;Bai L;Woodbury CJ;Ginty DD
通讯作者：
Ginty DD
影响因子：
2.4
作者：
Zhu YF;Henry JL
通讯作者：
Henry JL
影响因子：
64.5
作者：
Li L;Rutlin M;Abraira VE;Cassidy C;Kus L;Gong S;Jankowski MP;Luo W;Heintz N;Koerber HR;Woodbury CJ;Ginty DD
通讯作者：
Ginty DD
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA